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SRP118319
Danio rerio
3 Downloadable Samples
NextSeq 500
Description
Development of specialized cell types and structures in the vertebrate heart is regulated by spatially-restricted molecular pathways. Disruptions in these pathways can cause severe congenital cardiac malformations or functional defects. To better understand these pathways and how they regulate cardiac development and function we used tomo-seq, combining high-throughput RNA sequencing with tissue sectioning, to establish a genome-wide expression dataset with high spatial resolution for the developing zebrafish heart. Analysis of the dataset revealed over 1100 genes differentially expressed in sub-compartments. Pacemaker cells in the sinoatrial region induce heart contractions, but little is known about the mechanisms underlying their development and function. Using our transcriptome map, we identified spatially restricted Wnt/ß-catenin signaling activity in pacemaker cells, which was controlled by Islet-1 activity. Moreover, Wnt/ß-catenin signaling at a specific developmental stage in the myocardium controls heart rate by regulating pacemaker cellular response to parasympathetic stimuli. Thus, this high-resolution transcriptome map incorporating all cell types in the embryonic heart can expose spatially-restricted molecular pathways critical for specific cardiac functions. Overall design: To generate spatially-resolved RNA-seq data for the developing zebrafish hearts (2 days post fertilization), we cryosectioned 3 hearts, extracted RNA from the individual sections, amplified and barcoded mRNA using the CEL-seq protocol (Hashimshony et al., Cell Reports, 2012) with a few modifications. Libraries were sequenced on Illumina NextSeq using 75bp paired end sequencing. Sample Heart #1 is the primary sample. Heart #2 and #3 are biological replicates used for comparison.
Publication Title
Spatially resolved RNA-sequencing of the embryonic heart identifies a role for Wnt/β-catenin signaling in autonomic control of heart rate.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 17 Downloadable Samples
- Illumina HiSeq 2000
Description
We sequenced mRNA from three age groups (3months (3M), 24 months (24M) and 29 months (29M)) from the full hippocampus Overall design: There were two independent experiments: 3M vs 24M (n=5 to 6, single-end sequencing) and 3M vs 29M (n=3, paired-end sequencing))
Publication Title
De-regulation of gene expression and alternative splicing affects distinct cellular pathways in the aging hippocampus.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 52 Downloadable Samples
- IlluminaHiScanSQ
Description
UDP-sugars were identified as extracellular signaling molecules, assigning a new function to these compounds in addition to their well defined role in intracellular substrate metabolism and storage. Previously regarded as an orphan receptor, the G protein-coupled receptor (GPCR) P2Y14 (GPR105) was found to bind extracellular UDP and UDP-sugars. Little is known about the physiological functions of this GPCR. To study its physiological role we used a gene-deficient (KO) mouse strain expressing the bacterial LacZ reporter gene to monitor the physiological expression pattern of P2Y14. We found that P2Y14 is mainly expressed in pancreas and salivary glands and in subpopulations of smooth muscle cells of the gastrointestinal tract, blood vessels, lung and uterus. Among other phenotypical differences KO mice showed a significantly impaired glucose tolerance following oral and intraperitoneal glucose application. An unchanged insulin tolerance suggested altered pancreatic islet function. Transcriptome analysis of pancreatic islets showed that P2Y14 deficiency significantly changed expression of components involved in insulin secretion. Insulin secretion tests revealed a reduced insulin release from P2Y14-deficient islets highlighting P2Y14 as a new modulator of proper insulin secretion. Overall design: 10 samples from pancreatic islets isolated from wildtype mice; 10 samples from pancreatic islets isolated from P2Y14-knockout mice
Publication Title
The G protein-coupled receptor P2Y14 influences insulin release and smooth muscle function in mice.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 2 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Knockdown of HCLS1 mRNA in CD34+ hematopoietic cells resulted in a severe diminished in vitro myeloid differentiation which was in line with downregulation of a set of genes, e.g., of Wnt or PI3K/Akt signaling cascades. We performed microarrays to evaluate specific genes and signaling systems regulated by HCLS1 in hematopoietic cells.
Publication Title
Interactions among HCLS1, HAX1 and LEF-1 proteins are essential for G-CSF-triggered granulopoiesis.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment
View Samples- Mus musculus
- 69 Downloadable Samples
- Illumina HiSeq 2000
Description
Aging and increased amyloid burden are major risk factors for cognitive diseases such as Alzheimer''s Disease (AD). An effective therapy does not yet exist. Here we use mouse models for age-associated memory impairment and amyloid deposition to study transcriptome and cell type-specific epigenome plasticity at the systems level in the brain and in peripheral organs. We show that at the level of epigenetic gene-expression aging and amyloid pathology are associated with inflammation and impaired synaptic function in the hippocampal CA1 region. While inflammation is associated with increased gene-expression that is linked to a subset of transcription factors, de-regulation of plasticity genes is mediated via different mechanisms in the amyloid and the aging model. Amyloid pathology impairs histone-acetylation and decreases expression of plasticity genes while aging affects differential splicing that is linked to altered H4K12 acetylation at the intron-exon junction in neurons but not in non-neuronal cells. We furthermore show that oral administration of the clinically approved histone deacetylase inhibitor Vorinostat not only restores spatial memory, but also exhibits an anti-inflammatory action and reinstates epigenetic balance and transcriptional homeostasis at the level of gene expression and exon usage. This is the first systems-level investigation of transcriptome plasticity in the hippocampal CA1 region in aging and AD models and of the effects of an orally dosed histone deacetylase inhibitor. Our data has important implications for the development of minimally invasive and cost-effective therapeutic strategies against age-associated cognitive decline. In fact, our data strongly suggest to test Vorinostat in patients suffering from AD. Overall design: mRNA profile from aged (CA1 and liver) and APP/PS1 (CA1) animals treated with oral vehicle or SAHA for 4 weeks
Publication Title
HDAC inhibitor-dependent transcriptome and memory reinstatement in cognitive decline models.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina HiSeq 2000
Description
We sequenced mRNA from 24 samples extracted from mouse CA1 tissue to generate the first CA1-specific murine transcriptome and the first CA1-transcriptome in response to environmental novelty under normal and Kat2a-loss-of-function conditions. Overall design: Samples were divded in 4 groups: A: Control naïve (n=6), B: control novelty-exposed (n=5), C: Kat2a cKO naïve (n=6), D: Kat2a cKO novelty-exposed (n=7). Pairwise comparisons for AvsB, AvsC, BvsD and CvsD were performed using DESeq2.
Publication Title
K-Lysine acetyltransferase 2a regulates a hippocampal gene expression network linked to memory formation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
We sequenced small RNAs from 12 samples extracted from mouse CA1 tissue to generate the first CA1-specific murine miRNome under normal and Kat2a-loss-of-function conditions. Overall design: Samples were divded in 4 groups: A: Control (n=6), C: Kat2a cKO naïve (n=6)
Publication Title
K-Lysine acetyltransferase 2a regulates a hippocampal gene expression network linked to memory formation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
A mouse model for human small cell lung carcinoma (SCLC) has been developed based on evidence in human tumors that the tumor suppressor functions of RB and p53 are defective in more than 90% of SCLC cases. We also developed another mouse model also combines loss of p130 (Rbl2), an RB-related gene, with deletion of RB and p53. These two mouse tumors were shown to closely resemble human SCLC.
Publication Title
Loss of p130 accelerates tumor development in a mouse model for human small-cell lung carcinoma.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 43 Downloadable Samples
- Illumina HiSeq 2000
Description
Age-associated memory decline is due to variable combinations of genetic and environmental risk factors. How these risk factors interact to drive disease onset is currently unknown. Here we begin to elucidate the mechanisms by which post-traumatic stress disorder (PTSD) at a young age contributes to an increased risk to develop dementia at old age. We show that the actin nucleator Formin 2 (Fmn2) is deregulated in PTSD and in Alzheimer’s disease (AD) patients. Young mice lacking the Fmn2 gene exhibit PTSD-like phenotypes and corresponding impairments of synaptic plasticity while the consolidation of new memories is unaffected. However, Fmn2 mutant mice develop accelerated age-associated memory decline that is further increased in the presence of additional risk factors and is mechanistically linked to a loss of transcriptional homeostasis. In conclusion, our data present a new approach to explore the connection between AD risk factors across life span and provide mechanistic insight to the processes by which neuropsychiatric diseases at a young age affect the risk for developing dementia. Overall design: Role of Fmn2 gene for PTSD like phenotypes and impairments of synaptic plasticity.
Publication Title
Formin 2 links neuropsychiatric phenotypes at young age to an increased risk for dementia.
Sample Metadata Fields
Age, Cell line, Subject
View Samples- Sus scrofa
- 13 Downloadable Samples
- Porcine Gene 1.0 ST Array (porgene10st)
Description
Duchenne muscular dystrophy (DMD) is caused by mutations in the X-linked dystrophin (DMD) gene. The absence of dystrophin protein leads to progressive muscle weakness and wasting, disability and death. To establish a tailored large animal model of DMD, we deleted DMD exon 52 in male pig cells by gene targeting and generated offspring by nuclear transfer. DMD pigs exhibit absence of dystrophin in skeletal muscles, increased serum creatine kinase levels, progressive dystrophic changes of skeletal muscles, impaired mobility, muscle weakness, and a maximum life span of 3 months due to respiratory impairment. To address the accelerated development of muscular dystrophy in DMD pigs as compared to human patients, we performed a genome-wide transcriptome study of M. biceps femoris samples from 2-day-old and 3-month-old DMD and age-matched wild-type pigs. The transcriptome changes in 3-month-old DMD pigs were in good accordance with the findings of gene expression profiles in human DMD, reflecting the processes of degeneration, regeneration, inflammation, fibrosis, and impaired metabolic activity. The transcriptome profile of 2-day-old DMD pigs pointed towards increased protein and DNA catabolism, reduced extracellular matrix formation and cell proliferation and showed similarities with transcriptome changes induced by exercise injury in muscle. Our transcriptome studies provide new insights into congenital changes associated with dystrophin deficiency and secondary complications arising during postnatal development. Thus the DMD pig is a useful model to determine the hierarchy of physiological derangements in dystrophin-deficient muscle.
Publication Title
Dystrophin-deficient pigs provide new insights into the hierarchy of physiological derangements of dystrophic muscle.
Sample Metadata Fields
Age, Specimen part
View Samples